Efforts to prolong heart allograft survival by donor pretreatment have focused primarily on the donor animal. Ex-vivo organ pretreatment, though of greater potential utility has received little attention. Perfusion techniques developed in our laboratory have established predictable and reproduceable cardiac transplant survival results following hypothermic and normothermic ex-vivo heart preservation. These techniques will be used to investigate cardiac allograft survival in an established rat transplant model following graft and donor pretreatment with antithymocyte globulin, cytoxan, and the phytomitogen Concanavalin A. In vivo and in vitro techniques will be used to identify an optimal treatment regimen following isolated organ pretreatment with and without donor pretreatment and to investigate the immune mechanisms underlying pretreatment induced prolongation of heart allograft survival.